Histone deacetylases (HDACs) are a family of epigenetic regulators with emerging roles in both tumor and immune system biology. HDAC6 is a 131 KDa protein considered to be a key regulator of cytoskeleton dynamics and cell-cell interactions (Hubbert et al. Nature 417:455-458 (2002); Valenzuela-Fernandez, et al. Trends in Cell Biology 18:291-297 (2008)). Although this HDAC is predominantly cytoplasmic, studies have demonstrated its presence in nuclear extracts and its recruitment to gene promoter regions (Toropainen et al., J Mol Biol. 400:284-294 (2010)). HDAC6 has been reported to be over-expressed in several cancer types, including ovarian cancer, prostate cancer and acute myeloid leukemia (AML) (Aldana-Masangkay et al., J Biomed Biotechnol 2011:875824 (2010)).
HDAC6 has been implicated in the modulation of immune responses (Serrador et al., Immunity 20:417-428 (2004); Kalin et al., J Med Chem. (2012)). Recently, HDAC6 has been reported to modulate the acetylation of HSP90, a regulator of regulatory T-cell (Treg) suppressive activity (de Zoeten et al., Mol Cell Biol 31(10):2066-2078 (2011)). The use of HDAC6 as a target for generating and maintaining anti-tumor and peptide vaccination responses in vivo would be desirable. The subject matter disclosed herein addresses these desires and provide methods of targeting HDAC6 to improve immunotherapies.